Total Parenteral Nutrition Solutions Research Articles

Free oxygen radical-induced lipid peroxidation and antioxidant in infants receiving total parenteral nutrition

Objective Increased oxygen-derived free radical activity has been reported during total parenteral nutrition (TPN) in infants particularly linked to the fat infusion. It is possible that partial enteral feeding can ameliorate some of the complications of TPN. By this study we aimed to investigate free radical formation and antioxidant activity in term and preterm infants during TPN and/or enteral feeding. Study design We had 6 groups of term and preterm infants made up of 10 patients each. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured in all infants. Blood samples of infants receiving only TPN and TPN plus enteral feeding were measured on the 1st and 5th days, and 3 h after the end of lipid infusion. Results There was no difference between the term and preterm infants in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral, and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference. In addition, we compared baseline and 1st and 5th days of TPN therapy in both term and preterm infants fed only parenterally and enteral plus parenteral feedings. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than that of the levels of patients on parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the levels of vitamin C was significantly decreased, in term and preterm infants fed only parenterally, levels of vitamin E was increased, in term and preterm infants fed both parenterally and parenteral plus enterally. Also, when compared to their base line the SOD levels of the term infants detected on the 1st and 5th days were significantly high. Conclusion Free radical production is increased by the administration of TPN and may be linked to its adverse effects. It may be assumed that long-term complications of preterm infants receiving TPN may be reduced by further strengthening the antioxidant capacities of the TPN solutions.

Hepatic Copper in Patients Receiving Long-term Total Parenteral Nutrition

To assess the possibility of iatrogenic hepatic copper overload in adult patients on long-term total parenteral nutrition (TPN). TPN predisposes to hepatic copper accumulation through disturbances of the enterohepatic bile acid pool, but iatrogenic copper overload through TPN solutions may occur as well. Quantitative hepatic copper and multiple clinical, biochemical, and histopathologic parameters were compared between patients with long-term TPN associated liver disease (n = 28) and patients with drug-induced cholestatic liver disease (n = 10). Eighty-nine percent of TPN patients and all controls had mildly elevated hepatic tissue copper, but 29% of TPN patients had levels above the diagnostic threshold for Wilson's disease. Quantitative hepatic copper correlated positively with serum aspartate aminotransferase (P = 0.001, r = 0.59), total bilirubin (P < 0.001, r = 0.65), and direct bilirubin (P < 0.001, r = 0.63) in TPN patients, but not in controls. The amount of hepatic copper did not correlate with the duration of TPN (median, 1.9 years; range, 0.3-18.0 years) or serum copper levels. TPN patients with significant cholestasis accumulated more copper than patients with no or only minimal cholestasis (P = 0.002). Significant hepatic copper overload in TPN patients occurs through chronic cholestasis in TPN-associated liver disease and is independent from the total duration of TPN. Iatrogenic copper overload through trace elements in TPN solutions does not seem to be a significant factor.

Effects of arginine-containing total parenteral nutrition on N balance and phagocytic activity in rats undergoing a partial gastrectomy

The present study investigated the effect of arginine (Arg)-containing parenteral nutrition on phagocytic activity to elucidate the possible roles of Arg in the secretion of anabolic hormones and N balance in rats undergoing gastrectomy. Rats were divided into two experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN, the other group replaced 2 % of the total energy as Arg. After receiving TPN for 3 d, one-third of the rats in each experimental group were killed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 or 3 d after surgery. The results showed that there were no differences in N balance, plasma growth hormone and insulin-like growth factor-1 levels between the two groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Arg group than in the control group 1 d after surgery. There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the two groups at various time points. TNF-alpha levels in peritoneal lavage fluid were lower in the Arg group than in the control group on post-operative day 3. These results suggest that parenterally infused Arg enhances phagocytic activity and reduces the production of inflammatory mediators at the site of injury. However, Arg supplementation did not influence the secretion of anabolic hormones nor N balance in rats with a partial gastrectomy.

Effects of arginine supplementation on splenocyte cytokine mRNA expression in rats with gut-derived sepsis

To investigate the effects of arginine (Arg)-enriched diets before sepsis and/or Arg-containing total parenteral nutrition (TPN) after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis. Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. Plasma interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN-gamma) were not detectable 3 d after CLP. There were no differences in the distributions of CD45Ra(+), CD3(+), CD4(+), and CD8(+) cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-gamma was significantly higher in group 4 than in the other three groups. There was no difference in TNF-alpha mRNA expression among the four groups. The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Th1 and Th2 cytokines in the spleen of rats with gut-derived sepsis.

Effects of glutamine-containing total parenteral nutrition on phagocytic activity and anabolic hormone response in rats undergoing gastrectomy

To investigate the effect of glutamine (Gln)-containing parenteral nutrition on phagocytic activity and to elucidate the possible roles of Gln in the secretion of anabolic hormones and nitrogen balance in rats undergoing a gastrectomy. Rats with an internal jugular catheter were divided into 2 experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN (control), and in the other group, 25% of the total amino acid nitrogen was replaced with Gln. After receiving TPN for 3 d, one-third of the rats in each experimental group were sacrificed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 and 3 d, respectively, after surgery. Plasma, peritoneal lavage fluid (PLF), and urine samples were collected for further analysis. The Gln group had fewer nitrogen losses 1 and 2 d after surgery (d1, 16.6+/-242.5 vs -233.4+/-205.9 mg/d, d2, 31.8+/-238.8 vs -253.4+/-184.6 mg/d, P<0.05). There were no differences in plasma growth hormone (GH) and insulin-like growth factor-1 levels between the 2 groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Gln group than in the control group 1 d after surgery (A 1185+/-931 vs 323+/-201, P<0.05). There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the 2 groups at the baseline or on the postoperative days. No significant differences in interleukin-1beta or interleukin-6 concentrations in PLF were observed between the 2 groups. However, tumor necrosis factor-alpha level in PLF was significantly lower in the Gln group than in the control group on postoperative d 3. TPN supplemented with Gln can improve the nitrogen balance, and enhance macrophage phagocytic activity at the site of injury. However, Gln supplementation has no effect on phagocytic cell activity in the systemic circulation, GH and insulin-like growth factor-1 might not be responsible for attenuating nitrogen losses in rats with a partial gastrectomy.

Effects of glutamine supplementation on splenocyte cytokine mRNA expression in rats with septic peritonitis

To investigate the effects of glutamine (GLN)-enriched diets before and GLN-containing total parenteral nutrition (TPN) after sepsis or both on the secretion of cytokines and their mRNA expression levels in splenocytes of rats with septic peritonitis. Rats were assigned to a control group and 4 experimental groups. The control group and experimental groups 1 and 2 were fed a semipurified diet, while experimental groups 3 and 4 had part of the casein replaced by GLN which provided 25% of the total nitrogen. After rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), whereas the control group underwent a sham operation, at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. The control group and experimental groups 1 and 3 were infused with conventional TPN, while the TPN in experimental groups 2 and 4 was supplemented with GLN, providing 25% of the total nitrogen in the TPN solution. All rats were kiued 3 d after sham operation or CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. Most cytokines could not be detected in plasma except for IL-10. No difference in plasma IL-10 was observed among the 5 groups. The IL-2, IL-4, IL-10, and TNF-alpha mRNA expression levels in splenocytes were significantly higher in experimental groups 2 and 4 than in the control group and group 1. The mRNA expression of IFN-gamma was significantly higher in the GLN-supplemented groups than in the control group and experimental group 1. The proportion of CD45Ra+ was increased, while those of CD3+ and CD4+ were decreased in experimental group 1 after CLP was performed. There were no differences in spleen CD3+ lymphocyte distributions between the control and GLN-supplemented groups. GLN supplementation can maintain T-lymphocyte populations in the spleen and significantly enhance the mRNA expression levels of Th1 and Th2 cytokines and TNF-alpha in the spleen of rats with septic peritonitis.

Coloring and Blocking of In-line Filters when Total Parenteral Nutrition Solutions Are Supplemented with Vitamins and Trace Elements

Coloring and Blocking of In-line Filters when Total Parenteral Nutrition Solutions Are Supplemented with Vitamins and Trace Elements

Glutamine-supplemented total parenteral nutrition attenuates plasma interleukin-6 in surgical patients with lower disease severity

Previous reports have shown that decrease in plasma glutamine (Gln) level following major surgery may contribute to the state of immunosuppression. Gln supplementation improves the depletion of body Gln pool, and may have indirect effect on reducing proinflammatory mediator release. This study evaluated whether the effect of Gln dipeptide-enriched total parenteral nutrition (TPN) on postoperative cytokine alteration depended on the disease severity of surgical patients. Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/kg per d) and isocaloric (30 kcal/kg per d) TPN for 6 d. Control group (Conv) using conventional TPN solution received 1.5 g amino acids/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyl-L-glutamine (Ala-Gln)/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin (IL)-2, IL-6, IL-8, and interferon (IFN)-gamma analysis. Plasma IL-2 and IFN-gamma were not detectable. IL-6 concentrations were significantly lower on the 6(th) postoperative day in the Ala-Gln group than those in the Conv group in patients with APACHE II <=6, whereas no difference was noted in patients with APACHE II >6. There was no difference in IL-8 levels between the two groups. No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups (Ala-Gln -3.2+/-1.6 g vs Conv -6.5+/-2.7 g). A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-Gln group, whereas no such correlation was observed in the Conv group. TPN supplemented with Gln dipeptide had no effect on plasma IL-8 levels after surgery. However, Gln supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gln was administered.

Pharmacology Review

Extravasation or inadvertent infiltration of fluids into subcutaneous tissue from peripheral intravenous (IV) devices is a common adverse event in newborns. (1)(2) Although fluids occasionally extravasate from central venous lines, the complication is much more common from peripheral catheters, which are used widely in sick neonates. (3) This article focuses on extravasations from peripheral IV devices. Injury to the skin, even in a very immature neonate, results in an inflammatory response and heals by scar formation. (4) Although the scars from many of these injuries appear to improve with time, (5) tissue necrosis from extravasation injury could result in partial or complete skin loss, infection, and nerve and tendon damage, with the potential risk of permanent cosmetic and functional impairment. (6)(7)(8) The incidence of extravasations from Teflon® catheters has been reported to vary from 23% to 63%. (1) A recent survey of regional neonatal intensive care units in the United Kingdom recorded the prevalence of extravasation injury resulting in skin necrosis as 38 per 1,000 neonates, with 70% of these injuries occurring in infants of 26 weeks’ gestation or less. (2) The incidence of extravasation is related closely to the type of device used, insertion site, duration of therapy, infusate administered, patient activity, and gestational age. (1)(3)(9)(10) The fragility of the skin, particularly in the first 2 weeks after birth, and the lack of subcutaneous tissue in preterm neonates makes them uniquely susceptible to injury and skin loss. Extravasation may occur from the tip of the cannula or needle piercing the vessel wall. Alternatively, distal obstruction of the vein due to thrombosis or venoconstriction from irritation of the vessel wall may lead to increased back pressure and leakage from the entry point of the needle or …

Lack of enteral nutrition—effects on the intestinal immune system

Total parenteral nutrition (TPN) results in a loss of mucosal immune function by alterations in both phenotype and function of intraepithelial lymphocytes (IEL). We hypothesized that the observed changes with TPN administration are caused by the lack of enteral feeding, and not to the TPN solution itself. Mice received oral feeding (Control), TPN alone (TPN), or TPN plus oral feeding (TPN+Food). Mice were killed after 7 days, and bacteriological cultures from spleen, liver, and mesenteric lymph nodes obtained, with bacterial translocation (BT) being defined as a positive culture. IEL phenotype was analyzed by flow cytometry. IEL messenger RNA (mRNA) cytokine expression used reverse transcriptase polymerase chain reaction (RT-PCR). Apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. BT significantly (P < 0.05, with analysis of variance [ANOVA]) increased in the TPN group (53%) compared with Control (9%) and TPN+Food (14%) groups. TPN also resulted in a significant (P < 0.01) increase in epithelial cell apoptosis: TPN 7.6 +/- 1.1% versus Control 2.9 +/- 1.1% and TPN+Food 2.1 +/- 0.3% (mean +/- SD). Height of the villus-crypt complex was significantly decreased in TPN mice (315 +/- 16 microm) compared with Control (431 +/- 27 microm) and TPN+Food (421 +/- 26 microm) groups. IEL phenotypes significantly changed with TPN administration: CD4+ CD8- as well as CD4+ CD8+ subpopulations were reduced compared with Control or TPN+Food mice; as were the CD8alphabeta+ thymus-dependent, and CD8+ CD44+ mature IEL. IEL cytokine mRNA expression was also significantly altered with TPN: IL-2 and IL-10 expression declined, and IL-4 IL-6, interferon gamma (IFN-gamma), transforming growth factor beta-1 (TGF-beta1), and tumor necrosis factor-alpha (TNF-alpha) were increased, when compared with Control or TPN+Food mice. This study demonstrates that the major factor responsible for TPN-induced BT and IEL-changes is the lack of enteral feeding and not the administration of the TPN solution itself.

Metabolic and catheter complications of parenteral nutrition.

Since its introduction in the 1960s, total parenteral nutrition (TPN) has played a vital role in improving clinical outcomes for patients with acute and chronic illnesses. The evolution of TPN solutions and vascular access techniques, combined with an increased awareness and better understanding of the physiology of TPN, have improved the safety of this therapy. Nevertheless, complications are not uncommon and can be life threatening. This article provides an updated review on the metabolic and catheter complications associated with TPN.

Effects of lipid administration on liver apoptotic signals in a mouse model of total parenteral nutrition (TPN).

Lipids are an important component of total parenteral nutrition (TPN), contributing the largest caloric load per volume of solution and providing essential fatty acids necessary for survival. However, lipids are known to be causative factors in oxidative stress, which are expressed via the Bcl-2 family of proteins and/or Fas-mediated apoptosis in several tissues. Interestingly, we have recently observed an increase in hepatocyte apoptosis with administration of TPN. To address the mechanism of this apoptosis, we investigated the effects of parenteral lipid administration on apoptotic signaling in a mouse model. C57BL/6J male mice received physiologic saline and standard chow (control) or standard TPN solution with (TPN+L) or without lipid (TPN-L) emulsion. After 7 days of infusion, apoptosis increased in the TPN+L at a significantly higher rate compared with control and TPN-L groups ( p<0.05). Both TPN, with and without lipids, suppressed the pro-apoptotic signals Bid and Bcl-xs ( p<0.05). In contrast, TPN with lipid increased the expression of Fas and both the pro-apoptotic factor Bad and the anti-apoptotic factor Bcl-xl ( p<0.05). These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or suppress the ability of liver hepatocytes to regenerate.

Effects of glutamine supplementation on innate immune response in rats with gut-derived sepsis

The present study examined the effect of glutamine (Gln)-enriched diets before sepsis or Gln-containing total parenteral nutrition (TPN) after sepsis, or both, on the phagocytic activity and blood lymphocyte subpopulation in rats with gut-derived sepsis. Rats were assigned to a control group or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet; groups 3 and 4 had part of casein replaced by Gln. After feeding the diets for 10 d, sepsis was induced by caecal ligation and puncture (CLP); TPN was maintained for 3 d after CLP. The control group and groups 1 and 3 were infused with conventional TPN and groups 2 and 4 were supplemented with Gln in the TPN solution. All rats were killed 3 d after CLP or sham operation to examine their immune responses. The results showed that compared with the control group, the phagocytic activities of peritoneal macrophages were enhanced in groups 3 and 4, but not in groups 1 and 2. The proportion of CD3+ cells in group 1 was significantly lower (P<0.05) than that of the control group, whereas no differences were observed among the control and Gln-supplemented groups. The CD4+ cell proportion was significantly lower (P<0.05) in group 1 compared with the control group and groups 3 and 4. These findings suggest that Gln-enriched diets before CLP significantly enhanced peritoneal macrophage phagocytic activity, preserved CD4+ cells and maintained blood total T lymphocytes in gut-derived sepsis. However, parenteral Gln administration after caecal ligation and puncture had no favourable effects on modulating immune response in septic rats.

Vancomycin usage in central venous catheters in a neonatal intensive care unit.

We previously reported that vancomycin in hyperalimentation solution reduces catheter-related infections in the neonatal intensive care unit. Since June 1993 vancomycin (25 microg/ml) was routinely added to central venous catheter solutions, primarily hyperalimentation solution. Because the prophylactic use of vancomycin could lead to the emergence of resistant organisms, the decision to discontinue this practice was made in April of 1999. The use of vancomycin was reserved for documented infections with vancomycin-susceptible organisms. To compare catheter longevity, rate of laboratory-confirmed blood stream infections and total vancomycin exposure between two 18-month periods before and after the cessation of prophylactic vancomycin use. Data were evaluated for every neonate in whom a percutaneous central venous catheter was placed. There were 394 neonates enrolled. No statistically significant difference was identified between the two periods regarding the mean catheter days or number of catheters per patient. There was a higher rate of Gram-negative laboratory-confirmed blood stream infections during Period I in patients with percutaneous central venous catheters in place. There were more isolates of coagulase-negative staphylococci in Period II, resulting in more frequent vancomycin therapy institution and thus an overall increase in the amount of vancomycin used in that period Discontinuing the use of prophylactic vancomycin resulted in exposure of fewer neonates to vancomycin but a higher total amount of vancomycin used. The impact of low dose widespread exposure to vancomycin vs. high dose limited exposure on the microbiologic flora in the neonatal intensive care unit should be further examined.

Glutamine supplementation enhances mucosal immunity in rats with Gut-Derived sepsis

Objective Supplemental glutamine (Gln) has been demonstrated to improve the immunologic response and reduce mortality in rodents with sepsis. However, the effects of Gln on gut-associated lymphoid tissue function after infection and sepsis are not clear. We investigated the effects of Gln-supplemented diets before sepsis, Gln-enriched total parenteral nutrition (TPN) after sepsis, or both on the intestinal immunity in rats with gut-derived sepsis. Methods Male Wistar rats were assigned to control and four experimental groups. The control and experimental groups 1 and 2 were fed a semi-purified diet; in experimental groups 3 and 4, part of the casein in the diets was replaced with Gln. After feeding rats the respective diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP) in the experimental groups, whereas the control group underwent a sham operation; at the same time, the internal jugular vein of all rats was cannulated. All rats were maintained on TPN for 3 d. The control group and groups 1 and 3 were infused with conventional TPN, and groups 2 and 4 were given a TPN solution supplemented with Gln, which provided 25% of total amino acid nitrogen. All rats were killed 3 d after the sham operation or CLP. Intestinal immunoglobin A levels, total lymphocyte yields, and lymphocyte subpopulations in Peyer's patches were analyzed. Results Total Peyer's patch lymphocyte numbers were significantly higher in the Gln-supplemented groups than in the control group. Distributions of CD3 + and CD4 + in group 1 were significantly lower than those in the control group, whereas no differences were observed among the control and Gln-supplemented groups. Plasma immunoglobulin A levels were higher in the Gln-supplemented groups than the control group and group 1. Intestinal immunoglobulin A levels were significantly higher in groups 2 and 4 than in the control group and group 1. Conclusions Preventive use of a Gln-supplemented enteral diet before CLP or intravenous Gln supplementation after CLP have similar effects in promoting proliferation of total lymphocyte in gut-associated lymphoid tissue, enhancing IgA secretion, and maintaining T-lymphocyte populations in Peyer's patches. Gln administered before and after CLP did not seem to have a synergistic effect on enhancing mucosal immunity in rats with gut-derived sepsis.

Green coconut water for intravenous use: Trace and minor element content

AbstractGreen coconut water (GCW; liquid endosperm) is sterile and has been used in the past in remote locations and/or during armed conflicts as a short‐term intravenous hydration fluid. It is also conceivable to use GCW for total parenteral nutrition (TPN) under similar circumstances. Patients on TPN need elemental supplementation. Although data on the major elements (calcium, magnesium, potassium, sodium, and phosphorus) found in GCW are abundant, very limited information concerning trace and minor element content in GCW is available. The purpose of this study was to determine trace and minor element content in GCW. Major elements were arbitrarily defined as those with a GCW concentration in the mM range, as opposed to minor ones in the μM range and trace elements in the nM range. The values determined show the great variability typical for samples of plant origin. Under TPN conditions, GCW (1,000 mL/day) would be able to provide adequate supplementation of manganese (12 ± 5 μmol/L) and possibly zinc (6 ± 1 μmol/L) but not chromium (not detected, i.e., less than 9 nM/L) and copper (105 ± 100 nM/L). With respect to elements usually considered nonessential or even toxic, GCW compares favorably with commonly used TPN solutions, most notably for aluminium content (740 ± 360 nM/L) and cadmium (7 ± 4 nM/L). The levels of lead (150 ± 67 nmol/L) and barium (600 ± 300 nmol/L) were similar to those typically found in commercial TPN solutions. Those of strontium (8 ± 4 μmol/L) are higher but unlikely to be harmful. In conclusion, although GCW is not completely equivalent to high‐tech (and high‐cost) TPN solutions with trace element supplements, it still may provide sufficient support of at least some of the trace elements if used as a substitute. The GCW investigated by us is, at least, not toxic. However, our results for several trace elements are much lower than values previously reported in the literature, especially in coconuts from “polluted” areas. GCW from polluted soil might be easily toxic if used intravenously. J. Trace Elem. Exp. Med. 17:273–282, 2004. © 2004 Wiley‐Liss, Inc.

Effects of arginine supplementation on mucosal immunity in rats with septic peritonitis

Background: Supplemental Arginine (Arg) has been demonstrated to improve the immunologic response and reduce mortality in rodents with sepsis. However, the effects of Arg on gut-associated lymphoid tissue function after infection and sepsis are not clear. The aim of this study was to study the effect of Arg-supplemented diets before and Arg-enriched total parenteral nutrition (TPN) after sepsis or both on the intestinal immunity of rats with septic peritonitis. Methods: Rats were assigned to four groups. Groups 1 and 2 were fed a semipurified diet, while in the diets of groups 3 and 4, part of the casein was replaced with Arg. After feeding the experimental diets for 10 days, sepsis was induced by cecal ligation and puncture (CLP); at the same time, the internal jugular vein was cannulated. All rats were maintained on TPN for 3 days. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were given a TPN solution supplemented with Arg, which replaced 10% of the total amino acids. All rats were sacrificed 3 days after CLP. Intestinal immunoglobin (Ig) A levels, total lymphocyte yields, and lymphocyte subpopulations in Peyer's patches were analyzed. In vitro cytokine secretion by splenocytes and Peyer's patch lymphocytes were also measured. Results: Total lymphocyte yields in Peyer's patches, and small intestinal immunoglobulin A (IgA) secretion in group 4 were significantly higher than the groups 1 and 2. No differences were observed between groups 3 and 4. There were no differences in the interleukin (IL)-2 and interferon- γ levels among all groups when splenocytes were stimulated with mitogen. However, in vitro splenocyte IL-10 production in group 4 was significantly higher than those of groups 1 and 2, and had no difference from group 3. There were no differences in the ratios of B and T lymphocyte subpopulations in Peyer’s patches among all groups. Conclusions: Enteral Arg supplementation before sepsis tended to enhance total lymphocyte yields in Peyer's patches and intestinal IgA secretion. Arg administered both before and after CLP had a synergistic effect on improving intestinal immunity, possibly by enhancing systemic IL-10 secretion. However, intravenous Arg administration after CLP had no favorable effects on mucosal immunity in rats with septic peritonitis.

Enterocyte apoptosis and TPN-associated intestinal mucosal atrophy: a view of the chicken or the egg?

Enterocyte apoptosis and TPN-associated intestinal mucosal atrophy: a view of the chicken or the egg?

Arginine supplementation enhances peritoneal macrophage phagocytic activity in rats with gut-derived sepsis.

Previous reports have shown that arginine (Arg) enhances phagocytic activity of macrophages and is required for macrophage-mediated toxicity toward tumor cells. Few studies have addressed the importance of Arg supplementation on macrophage and neutrophil function after infection and sepsis. This study examined the effect of Arg-supplemented diets before and Arg-enriched total parenteral nutrition (TPN) after sepsis or both on the phagocytic activity of peritoneal macrophages and blood polymorphonuclear cells in rats with gut-derived sepsis. Male Wistar rats were assigned to 4 groups. Groups 1 and 2 were fed a semipurified diet, while groups 3 and 4 had part of the casein replaced with 2% of total calories as Arg. After the experimental diets were administered for 10 days, sepsis was induced by cecal ligation and puncture (CLP); at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 days. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg, replacing 10% of total amino acids in the TPN solution. Survival rates were recorded for 3 days after CLP, and all surviving rats were killed 3 days after CLP to examine their immune responses. Aerobic and anaerobic bacteria colony counts in peritoneal lavage fluid were significantly reduced, and the phagocytic activity of peritoneal macrophages was enhanced in groups 3 and 4 but not in the other 2 groups. There were no significant differences in the phagocytic activities of blood polymorphonuclear cells and survival rates among the 4 groups. Enteral Arg supplementation before sepsis significantly enhanced peritoneal macrophage phagocytic activity and reduced total bacterial counts in peritoneal lavage fluid. Arg administered before and after CLP seemed to have a synergistic effect on enhancing phagocytic activity and on bacterial clearance. However, IV Arg administration after CLP had no favorable effects on phagocytic activity or survival rates in rats with gut-derived sepsis.

Branched-chain Ketoacyl Dehydrogenase Deficiency: Maple Syrup Disease.

Classic maple syrup disease can be managed to allow a benign neonatal course, normal growth, and low hospitalization rates. The majority of affected infants that are prospectively managed have good neurodevelopmental outcome; however, acute metabolic intoxication and neurologic deterioration can develop rapidly at any age. Each episode is associated with a risk for cerebral edema, cerebrovascular compromise, and brain herniation. High plasma leucine and, possibly, alpha-ketoisocaproate are the principal neurotoxins in maple syrup disease. Plasma levels rise rapidly in association with net protein catabolism provoked by common infections and injuries. Transient periods of maple syrup disease encephalopathy appear fully reversible, leaving no clinically detectable neurologic sequelae. In contrast, prolonged amino acid imbalance, particularly if occurring during the critical period of brain development, leads to neuronal hypoplasia, a paucity of synapses, and undermyelination. Stagnated maturation and inadequate nutritional maintenance of brain structure have lifelong neurologic and behavioral consequences. Core elements of effective long-term therapy include screening and identification of asymptomatic newborns, frequent plasma amino acid monitoring, careful attention to branched-chain amino acid nurtriture, prevention of cerebral essential amino acid deficiencies, adequate provision of essential omega-3 class fatty acids and micronutrients deficient in commercial formulas, methods for home monitoring of metabolic control, and a commitment to lifelong therapy. Recognizing the risk for acute leucine intoxication depends on anticipating effects of common childhood infection and physiologic stresses on whole body protein turnover. Successful management of metabolic decompensation is based on the use of home sick-day regimens, rapid availability of branched-chain amino acid-free hyperalimentation solutions for hospitalized children, prevention of hyponatremia in patients with leucinosis, and frequent adjustments of intravenous therapies guided by plasma amino acid levels and indices of metabolic and clinical response.